December 4th, 2014

Sulfonylureas Tied to Higher Mortality in Diabetics

NEW YORK - Compared with other antidiabetic drugs, sulfonylureas may increase the risk of cardiovascular events and some may be particularly risky, according to Canadian researchers.

As Dr. Scot H. Simpson told Reuters Health by email, "Although there is a substantial amount of controversy regarding the cardiovascular safety of sulfonylureas, these drugs continue to be routinely used to help patients with type 2 diabetes."

"Our summary of the published evidence," he added, "would suggest there are important differences amongst sulfonylureas that clinicians should consider when selecting a drug from this class. For example, we believe glibenclamide (also known as glyburide) should be avoided in favour of other sulfonylureas, like gliclazide or glimepiride."

Dr. Simpson of the University of Alberta in Edmonton and colleagues used data from 18 controlled studies involving more than 167,000 patients to examine the risk of all-cause mortality, cardiovascular-related mortality and heart attacks with the drugs.

Nine percent of the patients died, ranging from 4% of gliclazide users to 7% of glibenclamide users to 23% of chlorpropamide users, the team reports in The Lancet Diabetes & Endocrinology, online October 23.

Network meta-analysis of all-cause mortality showed that compared with glibenclamide, the relative risk of death was 0.65 for gliclazide, 0.83 for glimepiride, 0.98 for glipizide, 1.13 for tolbutamide, and 1.34 for chlorpropamide.

For cardiovascular mortality the corresponding relative risk was 0.60 for gliclazide, 0.79 for glimepiride, 1.01 for glipizide, 1.11 for tolbutamide, and 1.45 for chlorpropamide.

Thus, the researchers conclude, "gliclazide and glimepiride were associated with a lower risk of all-cause and cardiovascular-related mortality compared with glibenclamide. Clinicians should consider possible differences in risk of mortality when selecting a sulfonylurea."

Commenting on the findings by email, Dr. Kevin M. Pantalone, author of an accompanying editorial, told Reuters Health that the new report is "a great summary of the available literature on this topic, and suggests that some sulfonylureas may be safer than others."

"Given that the individual sulfonylureas are available at a similar cost (cheap), it would seem inappropriate to use those which appear to be associated with a higher risk of cardiovascular events and/or mortality," added Dr. Pantalone of the Cleveland Clinic in Ohio. "We must rely on this type of study to guide our clinical decisions on this issue, as it is unlikely that the gold standard, a randomized controlled clinical trial, will ever be conducted."